Icariin Alleviates IL-1β-Induced Matrix Degradation By Activating The Nrf2/ARE Pathway In Human Chondrocytes

Objective: Osteoarthritis (OA) is characterized by progressive matrix destruction of articular cartilage. This study aimed to investigate the potential antioxidative and chondroprotective effects and underlying mechanism of Icariin (ICA) in interleukin-1 beta (IL-1 beta)-induced extracellular matrix (ECM) degradation of OA cartilage. Methods: Human chondrocyte cell line HC-A was treated with different doses of ICA, and then MTT assay and PI staining were used to estimate ICA-induced chondrocyte apoptosis. Intracellular ROS and superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured after treatment by IL-1 beta with or without ICA. The mRNA and protein expression levels of redox transcription factor Nrf2 and the downstream effector SOD-1, SOD-2, NQO-1 and HO-1 were assayed to explore the detailed mechanism by which ICA alleviates ECM degradation. Finally, to expound the role of Nrf2 in ICA-mediated chondroprotection, we specifically depleted Nrf2 in human chondrocytes and then pretreated them with ICA followed by IL-1 beta. Results: ICA had no cytotoxic effects on human chondrocytes and 10(-9) M was selected as the optimum concentration. ROS induced by IL-1 beta could drastically activate matrixdegrading proteases and ICA could significantly rescue the matrix degradation and excess ROS generation caused by IL-1 beta. We observed that ICA activated the Nrf2/ARE pathway, consequently upregulating the generation of GPX and SOD. Ablation of Nrf2 abrogated the chondroprotective and antioxidative effects of ICA in IL-1 beta-treated chondrocytes. Conclusion: ICA alleviates IL-1 beta-induced matrix degradation and eliminates ROS by activating the Nrf2/ARE pathway.